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- Pharmacology For Rifampicin + Isoniazid + Pyrazinamide
Rifampicin + Isoniazid + Pyrazinamide Pharmacology
Rifampicin + Isoniazid + PyrazinamideAbout Rifampicin + Isoniazid + PyrazinamideN/AMechanism of Action of Rifampicin + Isoniazid + PyrazinamideN/APharmacokinets of Rifampicin + Isoniazid + PyrazinamideN/AOnset of Action for Rifampicin + Isoniazid + PyrazinamideN/ADuration of Action for Rifampicin + Isoniazid + PyrazinamideN/AHalf Life of Rifampicin + Isoniazid + PyrazinamideN/ASide Effects of Rifampicin + Isoniazid + PyrazinamideN/AContra-indications of Rifampicin + Isoniazid + PyrazinamideN/ASpecial Precautions while taking Rifampicin + Isoniazid + PyrazinamideN/APregnancy Related InformationN/AOld Age Related InformationN/ABreast Feeding Related InformationN/AChildren Related InformationN/AIndications for Rifampicin + Isoniazid + PyrazinamideN/AInteractions for Rifampicin + Isoniazid + PyrazinamideN/ATypical Dosage for Rifampicin + Isoniazid + PyrazinamideN/ASchedule of Rifampicin + Isoniazid + PyrazinamideN/AStorage Requirements for Rifampicin + Isoniazid + PyrazinamideN/AEffects of Missed Dosage of Rifampicin + Isoniazid + PyrazinamideN/AEffects of Overdose of Rifampicin + Isoniazid + PyrazinamideN/A
RifampicinAbout RifampicinRifamycin derivative, Antituberculosis antibiotic.Mechanism of Action of RifampicinRifampicin is primarily bactericidal and has some bacteriostatic properties also. It acts by inhibiting DNA dependent RNA polymerase and thus stopping the expression of bacterial genes.M.tuberculosis requires DNA dependent RNA polymerase enzyme for the synthesis of RNA and protein. Without this enzyme bacteria cannot reproduce and they die.
Pharmacokinets of RifampicinAbsorption: Well absorbed orally, Distribution: Widely distributed, Metabolism: Metabolized in liver in to active desacetyl Rifampicin Excretion: Excreted mainly in bile & some extend in urineOnset of Action for RifampicinN/ADuration of Action for Rifampicin24 hoursHalf Life of Rifampicin2 - 5 hourSide Effects of Rifampicin1. Nausea
3. Epigastric distress
5. Pseudo membranous colitis
6. Acute renal failure
7. Hepato toxicity
17. Visual disturbance
19. Menstrual problems
Contra-indications of Rifampicin1.Hypersensitivity to the drug
6.As I.M. or S.C. injection
Special Precautions while taking RifampicinRenal impairment:
Use with caution
Use with caution
1.Use with caution in alcoholics
2.Use with caution in malnourished individuals
3.Stop the drug use in Purpura & Thrombocytopenia
Pregnancy Related InformationUse with cautionOld Age Related InformationUse with cautionBreast Feeding Related InformationUse with cautionChildren Related InformationAbove 5 years: May be used
Indications for Rifampicin1. Leprosy
3. Prophylaxis of meningococcal carriers
4. Prophylaxis of H. influenzae
Interactions for RifampicinRifampicin by inducing the hepatic microsomal enzymes may reduce the efficacy of the following drugs: Acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, chloramphenicol, clofibrate. Oral contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, beta blockers oestrogens, hydantoins, mexiletine, quinidine, sulfones, sulphonylureas, theophylline, verapamil.
Halothane: Hepatotoxicity and hepatic encephalopathy.
Isoniazid: Higher incidence of hepatotoxicity than with either agent alone.
Ketoconazole: Treatment failure of either ketoconazole or rifampicin.
Food: Interferes with absorption of rifampicin, therefore it should be taken on empty stomach.
Lab tests: Inhibits standard assays for serum folate and vitamin B12 (riboflavin). Transient abnormalities in liver function tests, reduced excretion of contrast media used for visualization of gall bladder.
Typical Dosage for RifampicinAdults: 0.45gm to 0.6gm single dose
Children: 10 to 20 mg/kg/day
Leprosy: 600mg orally once monthly
Adults: 600mg/day orally or I.V. as a single dose
Children: 10 to 20 mg/kg/day orally or I.V.as a single dose
600mg 12 hourly for two days
Children (1 to 2 years): 10 mg/kg
Children (below 1 year): 5mg/kg for two days
Schedule of RifampicinHStorage Requirements for RifampicinStore in a cool dry place.Protect from heat and light.Keep out of the reach of children.Effects of Missed Dosage of RifampicinTake the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.Effects of Overdose of RifampicinTreatment includes Gastric lavage, administration of activated charcoal, forced diuresis & bile drainage etc.
IsoniazidAbout IsoniazidHydrazine derivative, Antitubercular Agent.Mechanism of Action of IsoniazidIsoniazid is a bactericidal drug. I t inhibits the mycolic acid synthesis which is essential for the cell wall formation. It also inhibits DNA, RNA and protein synthesis and cell metabolism. As the results of these bacterial death occurs.Pharmacokinets of IsoniazidAbsorption: It is rapidly absorbed after oral administration.Distribution: It is very widely distributed in the body.Metabolism: It undergoes metabolism in the liver.Excretion:It is mainly excreted through urine and small amount excreted through bile, breast milk, sputum and saliva.Onset of Action for Isoniazid1 - 2 daysDuration of Action for Isoniazid1 dayHalf Life of Isoniazid1 - 4 hourSide Effects of Isoniazid1. Nausea
3. Gastric upset
4. Peripheral neuritis
5. Optic neuritis
13.JaundiceContra-indications of Isoniazid1. Hypersensitivity to Isoniazide
2. Drug induced hepatic diseaseSpecial Precautions while taking Isoniazid1.Renal impairment
4.EpilepsyPregnancy Related InformationContraindicatedOld Age Related InformationUse with cautionBreast Feeding Related InformationUse with caution
Children Related InformationMay be used
NEONATES: may be used
Indications for Isoniazid1.Tuberculosis (pulmonary &extra pulmonary)Interactions for IsoniazidAlcohol: Regular ingestion of alcohol is associated with higher incidence of INH-related hepatitis.
Aluminium Salts: Oral absorption of INH reduced leading to decreased serum levels.
Oral anticoagulants: Efficacy of oral anticoagulants increased.
Benzodiazepines: Activity of benzodiazepines that undergo oxidative metabolism is possibly increased.
Carbamazepine: Isoniazid hepatotoxicity & carbamazepine toxicity may occur from concurrent use.
Cycloserine: Increased cycloserine related CNS side effects, especially dizziness.
Disulfiram: Acute behavioural and co-ordination changes.
Enflurane: High output renal failure may occur.
Halothane: Hepatotoxicity and hepatic encephalopathy.
Hydantoins: Serum hydantoin levels increased leading to enhanced pharmacological and toxic effects.
Ketoconazole: Serum concentrations of ketoconazole decreased possibly leading to resistance to antifungal treatment.
Rifampicin: Higher incidence of hepatotoxicity than with either agent alone.
Food: Interaction with tyramine-containing foods since INH has MAOI activity.
Exaggerated response (headache, palpitation, sweating, hypotension, flushing, itching) to foods containing histamine (tuna, sauerkraut juice, yeast extract).
Typical Dosage for IsoniazidAdult: 200 - 300 mg once daily for 6 months to 24 months depending on the severity of infection
Children:5 - 10 mg / kg body weight / day for 6 months to 24 months depending on the severity of infection.
Schedule of IsoniazidHStorage Requirements for IsoniazidThe drug should be stored at room temperature .Keep away from heat, light and moisture. The vial should be kept at 2 - 8 degree Celsius.Effects of Missed Dosage of IsoniazidTake the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose.Continue the regular schedule.Do not double the dose.Effects of Overdose of IsoniazidGive supportive measures and treatment. Control seizure by giving Diazepam. Then Pyridoxine is administered followed by gastric lavage. Acidosis can be treated with sodium bicarbonate by parenteral administration. Forced diuresis and dialysis can be done if necessary.
PyrazinamideAbout PyrazinamideNiacinamide derivative, Antitubercular.Mechanism of Action of PyrazinamidePyrazinamide is a bactericidal or bacteriostatic drug depending on the drug concentration at the infection site and the susceptibility of organism. Pyrazinamide is a prodrug and it undergoes hydrolysis and forms the active metabolite Pyrazinoic acid. It disrupted membrane energetic and inhibited membrane transport function at acid pH in Mycobacterium tuberculosis. The anti-mycobacterial activity appears to depend on conversion of the drug to Pyrazinoic acid. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates Pyrazinamide to Pyrazinoic acid, and the vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. Experimental evidence suggests that Pyrazinamide diffuses into M. tuberculosis in a passive manner, is converted into Pyrazinoic acid by pyrazinamidase and because of an inefficient efflux system, accumulates in huge amounts in the bacterial cytoplasm. The accumulation of Pyrazinoic acid lowers the intracellular pH to a suboptimal level that is likely to inactivate a vital target enzyme such as fatty acid synthase.Pharmacokinets of PyrazinamideAbsorption: It is well absorbed after oral administration.Distribution: It is very widely distributed mainly to tissues and fluids. It has good penetration in CSF. Only 50 % is distributed in protein bound form.Metabolism: It undergoes hydrolysis in the liver.Excretion: It is excreted mainly in the urine
Onset of Action for Pyrazinamide30 - 60 minutesDuration of Action for Pyrazinamide12-16 hours.Half Life of Pyrazinamide9 - 10 hoursSide Effects of Pyrazinamide1. Nausea
15. Sideroblastic anaemiaContra-indications of Pyrazinamide1. Hypersensitivity to Pyrazinamide
2. Severe hepatic diseases
3. Acute gout
Special Precautions while taking Pyrazinamide1. Diabetes mellitus
2. Renal impairment
3. GoutPregnancy Related InformationUse with cautionOld Age Related InformationUse with caution.Breast Feeding Related InformationUse with cautionChildren Related InformationMay be used
Indications for PyrazinamideTuberculosis.Interactions for PyrazinamideUricosurics: Antagonism of effect of probenecid and sulphinpyrazone.
INH: Significantly reduces INH serum concentrations.
Anti-diabetic agents: Affects control of diabetes in diabetics.
Typical Dosage for PyrazinamideAdult:15 - 30 mg / kg body weight/ day in single dose, maximum dose up to 3 g/ day or 50 - 70mg / kg body weight/ twice weekly
Children: Same as adult dose
Schedule of PyrazinamideHStorage Requirements for PyrazinamideStore the drug at 15 - 30 degree C in a tightly closed container. Protect from heat and light. Keep out of the reach of children.Effects of Missed Dosage of PyrazinamideTake the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.Effects of Overdose of PyrazinamideGive supportive measures and symptomatic treatment. Drug can be removed from the body by gastric lavage or by inducing emesis. Absorption of the drug can be reduced by administration of activated charcoal.
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